The objective of this research is to establish the role of the oral flora in affecting the host's response to possible carcinogens in the environment. Concern about exposure to possible mutagenic and carcinogenic agents has stimulated the development of test systems to warn of the presence of such compounds. Metabolic reactions of potential significance to carcinogenesis (azo, nitro, reduction; nitroso formation and degradation) will be examined to ascertain whether the oral flora is capable of playing a role similar to that of the intestinal flora as being important in the activation or deactivation of potential carcinogens. Initially dental therapeutics and tumorigenic agents in cigarettes will be tested because of their chronic exposure and application to the oral mucosa. DNA damage that may result from exposure to various dental therapeutic agents (chemicals) will be quantitated using the Ames in vitro mutagen test system. This method maximizes detection of DNA damage by Salmonella typhimurium mutants in vitro. The usefulness and sensitivity of the above in vitro method has been improved by infecting germ-free rats with the Salmonella mutant. This model incorporates bacterial metabolism and mammalian physiology by maintaining the bacterial mutants in the oral cavity and gastrointestinal tract. This is advantageous since these bacteria would then function as a biological probe, indicating the DNA damaging ability of chemicals under conditions present in the actual animal. An important advantage of this model is that the bacteria normally present in the oral cavity and gastrointestinal tract can be added into the rat in selected ways so their role in carcinogenesis (vis-a-vis mutagenesis) can be evaluated under well-controlled conditions. Using these techniques we hope to identify potential carcinogens (therapeutic agents) as mutagens and determine the role of the oral and intestinal flora in the carcinogenic process.